On May 10th, the U.S. District Court for the District of Columbia ruled in FDA’s favor in a case filed last July by Graceway Pharmaceuticals, LLC (“Graceway”) stemming from the Agency’s January 2010 denial of a Graceway citizen petition and approval of a generic version of Graceway’s ALDARA (imiquimod) Cream, 5%. In granting FDA’s Motion for Summary Judgment and denying Graceway’s Motion for Summary Judgment, Judge Reggie B. Walton’s 21-page decision gave FDA another feather for its cap insofar as court challenges to FDA generic drug bioequivalence and ANDA approval decisions are concerned.

As we previously reported (here and here), the primary issue raised in the Graceway petition and lawsuit was whether a generic applicant can demonstrate bioequivalence for a multi-indication Reference Listed Drug (“RLD”) with a comparative clinical trial in just one indication, and whether FDA’s approval of a generic version based on a trial in one indication violated the FDC Act and the Administrative Procedure Act (“APA”). Graceway requested in its petition that FDA refuse to approve ANDAs for generic versions of ALDARA Cream unless such applications contain, among other things, data from bioequivalence studies conducted in patients with each of ALDARA’s three approved indications – actinic keratoses (“AK”), primary superficial basal cell carcinoma (“sBCC”), and external genital and perianal warts/condyloma acuminata (“EWG”). FDA denied the petition (concluding that a well-designed study in AK will suffice to show bioequivalence of a generic version of ALDARA for all indications), approved an ANDA, and the lawsuit followed.

FDA has long held – see e.g., Docket No. FDA-1995-P-0044 – that a clinical endpoint bioequivalence study in one indication for a multi-indication RLD can suffice as proof of bioequivalence in another indication when the indications are “related” and involve the “same site of action.” Indeed, in 2009, the U.S. District Court for the Central District of California ruled that FDA’s April 2008 denial of a citizen petition and decision to approve a generic version of EFUDEX (fluorouracil) Topical Cream, 5%, under somewhat similar circumstances to generic ALDARA Cream did not violate the APA – see our previous post here.

Graceway alleged in its July 2010 Complaint that:

FDA’s decision not to require bioequivalence studies in patients with [EWG] was based on its unsupportable conclusion that genital warts are “related” to and share the same “site of action” as the other two conditions treated by Aldara, both of which result from sun exposure. This determination was unsupported by – and in fact, contrary to – basic science, common sense, and the agency’s previous actions in similar situations. While Graceway is not contesting for the purposes of this lawsuit that AK and [sBCC] may be “related” in the sense that both result from sun exposure, neither has anything in common with genital warts, which appear in the pubic area and are caused by an infectious disease – a sexually-transmitted virus. [(internal citation omitted)]

FDA shot back that its conclusions “were based upon reasoned scientific analysis, and were therefore not arbitrary, capricious, or otherwise contrary to law.” Graceway also made much hay out of an apparent disagreement between FDA’s CDER Dermatology Division and the Office of Generic Drugs (“OGD”) concerning study requirements. That conflict was ultimately resolved in favor of OGD’s position, which was relayed in the citizen petition response.

Quickly dispensing with any issues raised by Graceway about the internal disagreement at FDA, but nevertheless noting that “the internal disagreement between the different divisions of the FDA is certainly not irrelevant, but neither is it the dispositive proof of arbitrary and capricious action that the plaintiff seems to believe it is,” Judge Walton examined the extent to which FDA’s petition response contained well-reasoned explanations. On both of Graceway’s “site of action” and “relatedness” arguments, Judge Walton ruled in FDA’s favor, concluding that “because the FDA addressed each argument raised in the plaintiff's Citizen Petition, explained its conclusion with respect to each argument, and cited the scientific literature on which it relied, the FDA's Response denying the plaintiff's Citizen Petition was not arbitrary, capricious, or otherwise contrary to law, and therefore does not violate the APA.”